This study proposes to investigate the relationship of nuclear RNA metabolism in specific brain subregions to the behavioral effects of various psychotropic agents. It is divided into two interrelated sections. Firstly, alterations of nuclear and neuronal nucleolar RNA metabolism will be investigated in whole brain and in brain subregions: 1) during states of inhibition of ribosomal RNA synthesis and processing produced by actinomycin D and toyocamycin, respectively, 2) during acute and chronic treatment with psychotropic drugs including morphine, phenobarbital, amphetamine, lysergic acid diethylamide, delta 9-tetrahydrocannabinol and chlorpromazine. Rapidly labeled RNA will be extracted from the neuronal nuclei and nucleolar enriched fractions and analyzed by acrylamide-agarose gel electrophoresis to obtain S45 RNA, the ribosomal precursor. Various physicochemical parameters of nuclear and nucleolar RNA metabolism will be studied including, 1) RNA polymerase activity of aggregate and solubilized enzyme, 2) stability of newly formed RNA and 3) electrophoretic mobility, turnover, and base composition of the RNA. Secondly, alterations in nuclear RNA metabolism related to growth and development will be investigated in normal brain and in rats treated as above. These studies will be carried out in 7-9 day old, 20 day old and 90 day old male rats. The electron microscope will be used as an index of purity of nuclei and to study the morphology of brain nuclear subfractions during normal rat growth and during treatment by the above agents.